RESUMO
OBJECTIVES: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. RESULTS: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif- eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and ß-catenin) expression changed in SiHa cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Proteínas de Ciclo Celular/genética , Proteínas de Membrana/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Apoptose/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , RNA Interferente Pequeno/genética , Transfecção , Neoplasias do Colo do Útero/metabolismoRESUMO
PURPOSE OF INVESTIGATION: To provide a systematic overview to understand the mechanism of ovarian cancer. MATERIALS AND METHODS: Data of GSE14407 downloaded from Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. Gene ontology and pathway enrichment analysis were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the authors constructed the protein-protein interaction (PPI) network and co-expression networks by Cytoscape. RESULTS: A total 1,442 genes were identified to be differentially expressed. Regulatory effects of DEGs mainly focused on cell cycle, transcription regulation, and cellular protein metabolic process. Significant pathways were determined to be p53 signaling pathway, amino sugar, and nucleotide sugar metabolism. The most significant transcription factor was aryl hydrocarbon receptor nuclear translocator (ARNT). Abnormal spindle-like microcephaly-associated protein (ASPM), Aurora kinase (AURKA), Cyclin-A2 (CCNA2), G2/mitotic-specific cyclin-B1, (CCNB1), and Cyclin-dependent kinase 1 (CDK1) were significant nodes in PPI network. CONCLUSION: The significant genes and pathways show potential targets for the treatment of ovarian cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Proteína Quinase CDC2 , Carcinoma Epitelial do Ovário , Biologia Computacional , Ciclina A2/genética , Ciclina A2/metabolismo , Ciclina B1/genética , Ciclina B1/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Bases de Dados Genéticas , Feminino , Humanos , Terapia de Alvo Molecular , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/terapia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
This study evaluated the influence and mechanism of different Munziq doses on myocardial ischemia reperfusion injury (MIRI) rats with abnormal savda. Wistar rats (N = 96) were divided into the following 8 groups (12 rats each): ischemia-reperfusion (I/R) model group, high-dose, medium-dose, and low-dose Munziq groups, normal I/R group, sham model group, normal sham group, and Atorvastatin group. Changes in heart physiology and myocardial morphology after injury with MIRI were monitored in each group. Heat shock protein 70 (HSP70) and calcitonin gene-related peptide (CGRP) protein expression and serum concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, and IL-8 were detected by using western blot and ELISA methods, respectively. The large-dose Munziq group showed the most significant changes. The VPC incurring time was not delayed in the small-dose group, but the accumulative time was significantly reduced (P < 0.01). The ventricular tachycardia incurring time did not differ significantly between groups. Compared with the normal sham surgical group, the I/R groups showed significant increases in HSP70 and CGRP expression (P < 0.01) and MDA, IL-6, and IL-8 concentrations (P < 0.05) and a significant decrease in the SOD concentration (P < 0.05). Compared with the I/R groups, Munziq intervention significantly enhanced HSP70 and CGRP expression (P < 0.01), significantly decreased MDA, IL-6, and IL-8 concentrations (P < 0.05), and significantly increased the SOD concentration (P < 0.05). In conclusion, Munziq intervention improves cardiac physiological function, increases the expression of HSP70 and CGRP, and decreases the inflammatory reaction in MIRI model rats.